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Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage

Artikel i vetenskaplig tidskrift
Författare Anna Thorfve
Tilo Dehne
Anders Lindahl
Mats Brittberg
Axel Pruss
Jochen Ringe
Michael Sittinger
Camilla Karlsson
Publicerad i Cartilage
Volym 3
Nummer/häfte 1
Sidor 43-57
ISSN 1947-6035
Publiceringsår 2012
Publicerad vid Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin
Institutionen för kliniska vetenskaper, Avdelningen för ortopedi
Sidor 43-57
Språk en
Länkar dx.doi.org/10.1177/1947603511414178...
Ämnesord Human Cartilage, Osteoarthritis, WNT signaling
Ämneskategorier Cell- och molekylärbiologi, Ortopedi

Sammanfattning

Objective: It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue. Methods: Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes. Results: Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca2+/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers. Conclusions: WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca2+/WNT pathway was activated in OA cartilage.

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